Renin-Angiotensin System Inhibitor (RASi) Use and Atrasentan in IgAN: Post Hoc Analysis from the ALIGN Trial
Bibliographic record
Abstract
Background: Atrasentan, a highly selective ETA receptor antagonist, significantly reduced proteinuria vs placebo (pbo) in patients (pts) with IgAN in the ALIGN (NCT04573478) interim analysis. Atrasentan (VANRAFIA®) received US FDA accelerated approval for proteinuria reduction in adults with primary IgAN at risk of rapid disease progression. Given global variability in RASi regimens, a post hoc analysis assessed the ALIGN Week 36 primary endpoint data by baseline (BL) RASi class and dose. Methods: ALIGN is an ongoing, Phase III, randomized, double-blind study of atrasentan 0.75 mg/day vs pbo in adults with IgAN on stable, maximally tolerated RASi. Change from BL in 24-hour urine protein–creatinine ratio (24h-UPCR) at Week 36 was assessed by RASi class and by percentage of the maximum labeled dose (MLD) of RASi (≤50% or >50%) prescribed at BL. Results: Pts received two-thirds (69.0%) of MLD RASi on average. Of 270 pts, 54.4% received ≤50% MLD RASi and 41.1% received >50% MLD RASi. At BL, 71.1% and 27.4% of pts, respectively, were on an angiotensin II receptor blocker (ARB) and angiotensin-converting enzyme inhibitor (ACEi); 23 distinct ARBs and 10 distinct ACEis were prescribed. At Week 36, a 24h-UPCR reduction of 39.3% (95% CI 30.3, 47.0) was seen in the atrasentan arm for pts on ≤50% MLD RASi and a reduction of 37.5% (95% CI 27.4, 46.2) was seen in the atrasentan arm in pts on >50% MLD RASi (Figure). 24h-UPCR reductions of 36.8% (95% CI 28.9, 43.7) and 41.5% (95% CI 29.1, 51.7) were seen in the atrasentan arm for pts on ARB and ACEi, respectively. Conclusion: Atrasentan led to clinically meaningful proteinuria reduction regardless of BL RASi class (ARB or ACEi) and dose. These data support the potential for atrasentan to be seamlessly added onto a variety of existing RASi treatment and dose regimens. The results add to the available data for atrasentan, which has the potential to be a foundational therapy in IgAN. Funding: Commercial Support - Novartis
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.008 | 0.005 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.005 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".